Interplay of Type 2 Inflammation, Small Airway Dysfunction, and Patient-Reported Outcomes in Treatment-Naīve Uncontrolled Asthma: A Retrospective Primary Care Analysis

Background: Effective initial asthma treatment in primary care requires a comprehensive assessment of airway inflammation and lung function impairment, including small airway dysfunction (SAD). We investigated the prevalence of type 2 (T2) inflammation and SAD in treatment-naīve patients with uncontrolled asthma who received primary care, and assessed the utility of the Asthma Control Questionnaire-5 (ACQ-5) as a potential indicator of these factors. Methods: This single-center retrospective study enrolled treatment-naīve adults who presented with uncontrolled asthma (ACQ-5 score ≥ 1.5) between April 2020 and March 2022. T2 inflammation was assessed using blood eosinophil count (bEOS), fractional exhaled nitric oxide (FeNO), and total immunoglobulin E (IgE) levels. Patients with bEOS ≥ 300 cells/μL and FeNO ≥ 50 ppb were designated "T2-high." SAD was defined as a forced expiratory flow between 25% and 75% of the vital capacity percentage predicted value (FEF25-75%pred) < 65%. Results: Among 192 patients, 87% exhibited an elevation in at least one T2 biomarker, with 47% meeting the T2-high criteria. An ACQ-5 score ≥ 3.0 significantly predicted T2-high status (odds ratio: 2.62, 95% confidence interval: 1.46-4.69, p = 0.00127). SAD was identified in 52% of patients, with ACQ-5 scores showing a strong negative correlation with FEF25-75%pred (ρ = -0.583, p < 0.0001), particularly for nocturnal awakening score (ρ = -0.728, p < 0.0001). Conclusions: Our findings revealed a high prevalence of T2 inflammation and SAD in treatment-naīve patients with uncontrolled asthma who received primary care. The ACQ-5 demonstrates potential as a practical screening tool for these pathophysiological features, offering valuable guidance for initial treatment decisions where advanced diagnostic capabilities may be limited.